Unit 4 AOS1

infectious disease

an illness caused by the invasion of the body by a pathogen

pathogen

an infectious biological agent that causes disease

pathogens can be

cellular: bacteria, fungi, protozoa, parasite

non-cellular: prions, viruses

Pathogens cause a disease by

• invading the tissue as they reproduce

• producing enzymes

• inhibiting normal metabolism or function

• production of toxins

• competing for nutrients

pathogens enter their hosts by:

• contaminated food

• contaminated water

• droplets or suspended in the air

• as spores in the air

• carried by animals

• through wounds

• in body fluids such as blood

antigens

Any molecule, usually a protein, that can elicit an immune response and can be recognised by a specific complementary antibody or T cell receptor

where are antigens found and what can they act a

• found on the surface of cells

• bacterial toxins float freely in body fluids

• molecules on surfaces of pathogens can act as antigens, as can chemicals and toxins

what must organisms distinguish foreign antigens from

‘self’ markers

Major Histocompatibility complex (MHC)

Protein markers found on cell surfaces unique to each individual at are important in distinguishing self cells from non-self cells

Class 1 MHC markers

located on the surface of all nucleated body cells

Class 2 MHC markers

located on antigen-presenting cells where antigen fragments are present

Bacteria

• unicellular prokaryotes

• unique characteristics:

  • few bacteria are pathogenic (those that are usually produce toxins)

  • many bacteria form normal microfora found on healthy humans

  • oxygen requirments

  • nutritional needs

• infect host to exploit food potential of host’s body tissues

• reproduce by binary fission

• treatment: antibiotics

Fungi

Unicellular or Multicellular eukaryotes

• e.g. molds, yeasts, tinea, thrush

• secrete digestive enzymes

• reproduce by forming spores that survive in extreme condition

• treatment: anti-fungals

Protozoa

Unicellular eukaryotes

• many go through various stages of life in multiple hosts and undergo antigenic variation

• usually reproduce asexually, can produce sexually

• treatment: antiprotozoals

Multicellular Parasites

• parasites infect plants and animals

• parasites include flat worms such as tapeworms and insects such as ticks and lice

• reproduce asexually

Viruses

Non-cellular, intracellular parasites

• most only able to invade a specific cell type of only one host species

• composed of either RNA or DNA enclosed in a protein coat called a capsid

• some have a lipid envelope (washing hands kills this part)

• use cellular machinery of host cells to replicate (take over host cell)

• antigenic drift: thus a virus is not recognised by the immune system at a later time

• treatment: antivirals

antigenic drift

some viruses have) constant minor changes to surface antigens

virions

viral particles that enter a host cell either by receptor mediated fun or by endocytic pathways

once new viruses assembled, released from host cells

Prions

Smallest infectious agents, non-cellular, composed of just protein (no genetic material)

• prions are abnormal forms of a normal brain cell protein. (abnormal proteins)

  • caused due to mutation in the gene coding for PrP causing protein to fold incorrecly

• induce normal proteins to fold in an abnormal manner

• rapid gowth of prions causes vacuoles and protein to aggregate, causing clumps of misfolded proteins to aggregate in the brain, death

nature of prions

a shape change transforms harmless protein into its infectious prion form

• mainly beta pleated sheets (primary structure still the same)

  • resistant to denaturation and proteases

• due to similarity between normal protein inate immune response ineffective no APC’s so no adaptive

prions summary

no treatment

modes of transmission:

• misfolded protein physically interacts with regular healthy protein and corrupts it

• folds incorrectly

• now two misfolded proteins

Plants Physical Defenses

Waxy cuticle

Thickened Bark

Trichomes: hair on stem of a plant - catch pathogens

Intact Epidermis

Plants Chemical Defenses

• secretion of toxins harmful to pathogens

• secrete antimicrobial compounds (defensins)

plant show systemic acquired resistance (hightened state of readiness)

Plants Microbial Defenses

• beneficial soil and surface bacteria

  • prevent colonisation by other microbial groups by:

    • altering soil conditions to deter establishment

    • competing for space and nutrients

    • producing antimicrobial compounds

• roots of plants have good bacteria and fungi - breaks down nutrients, provides nutrients to plant

First Line of Defense

The physical and chemical barriers that keeps pathogens from entering the body of a living thing

what do barriers to infections form

the first line of non-specific defense, they act in the same way, regardless of the pathogen

Physical Barriers

impede or prevent the entry of pathogens into the body

• Intact skin

• Wax and hairs

• cilia, eyelashes

• reflexes

• flow fluids (tears)

• mucus

Chemical Barriers

inhibit the growth or development of pathogens

• lysozymes and toxic metabolite in tears, sweat, saliva that inhibit growth of bacteria and fungi

• stomach acid, digestive enzymes

Microbiological Barriers

prevent the growth or colonization of pathogens by competing for nutrients or altering conditions

• good bacteria/bugs in and around body that help to protect you from the pathogenic kinds

• bacteria on skin (microflora) secrete oils and enzymes that helps keep skin intact, so if you have any bad bacteria on the surface it can kill them

The Second Line of Defense

involves non-specific innate defenses you are born with that are the same regardless of the pathogen species. They react quickly and involves cells and molecules

• no immunological memory produced

leukocyte

general term for white blood cell

what do leukocytes have

toll like receptors that recognise pathogen associated molecular patterns (PAMPs, conserved non-self molecules common to a range of pathogens (thus non specific)

Phagocyte

leukocyte that engulfs pathogens and debris and digests them by phagocytosis

• neutrophils, macrophages, dendritic cells

Phagocytosis Process

• the phagocyte engulfs antigen/pathogen/something it recognises foreign

• stored in a phagosome

• Phagosome fuses with a lysosome to become a phagolysosome

• enzymes safely contained in lysosome are able to be exposed to the pathogen and destroys it

• contents released by exocytosis

Neutrophils

• make up majority of red blood cells (b/c try to compensate w limited abilities of dying after phagocytosing by having lots of them)

• they release toxic antimicrobial compounds called defensins that disrupt pathogen cell membranes and some cytokines

• phagocytose

Macrophages

• found in most body tissues

• release cytokines to coordinate immune response

• phagocytose

• antigen presenting cells

• act more slowly and clean up debris (better lifespan)

Dendritic Cells

• found on skin and mucus surfaces

• main antigen presenting cells

• large surface area

• phagocytose

Natural Killer Cells

a type of leukocyte attracted by chemical cytokines made by phagocytes

• recognise a lack of or damage to MHC 1 on virus infected cells and cancer cells (not free pathogens)

• if insufficient binding to MHC1 they release perforin which punches holes in the membrane and secretes granzymes that enter through the holes triggering apoptosis

• DONT TARGET NON-CELLULAR

Eosinophils

a type of granulocyte that contains granules (secretory vesicles filled with defensive molecules released during an immune response)

• secretes a range of toxic chemicals: cytokines, chemokines, enzymes

• target large pathogens such as worms, flukes that are too large for phagocytosis

• involved in allergic responses

Apoptosis

regulated cell death, which is necessary to get rid of old, damage or unnecessary cells

Cytokines

A group of signaling proteins/molecules secreted by white blood cells that coordinate the immune response enabling communication between WBC’s

when are cytokines released

released in response to cell damage or the presence of pathogens

what type of response do cytokines trigger

specific and non specific responses

• interleukins regulate immune response

• chemokines activate and attract phagocytes via chemotaxis

Complement Proteins

proteins produced in the liver present in body fluids that circulate the blood in inactive form.

when are complement proteins activated

activated when bound to pamps or antibody-antigen complexes leading to a cascade of reactions that results in effector molecules that perform:

• opsonisation

• chemotaxis

• lysis

opsonisation

coat pathogens, tagging them for destruction by phagocytosis

chemotaxis

chemical attractions

• coat antigen/target and emits a sign by gathering near the pathogen

• attracts phagocytes, granulocytes and other immune cells

lysis

complement proteins can join together on the surface of pathogens forming a membrane attack complex that punches holes in membranes causing lysis by the sudden influx of fluid into the pathogen, causing it to burst

difference between opsonisation and chemotaxis

chemotaxis attracts the immune cells to the site, when they get there opsonisation enhances the phagocytosis

Interferons

A class of cytokines produced by virally infected cells to inhibit viral reproduction

• activate neighboring cells to produce enzymes that break down viral RNA and proteins

• Change the membrane of neighboring cells so virus penetration is more difficult

• induce apoptosis in neighboring infected cells

• attract NK cells

overall: warn surrounding cells that they can apoptose, move away, making antivirals

Inflammation

• a rapid, response to tissue damage or microbial infection characterized by pain, redness, heat and swelling.

• triggered by cytokines and complement

• tissue damage releases DAMPS which stimulate mast cells

Steps in Inflammation Response

• Invasion of Pathogen through breach of intact skin/first line of defense

• damaged cells release cytokines which stimulates mast cells

• mast cells detect damage causing histamine to be released via exocytosis

• histamine promotes vasodilation (bringing more blood to the area, so immune cells get there faster) and increased permeability of blood vessels (leak allowing WBC’s and fluid w immune agents to leave blood and enter tissue)

• immune cells enter tissue from bloodstream via chemotaxis

• phagocytes phagocytose pathogens to clear the infection

• resus in redness (D), swelling (I), pain (I), warmth (D)

Fever

a regulated increase in body temperature above the normal range (365) due to macrophages releasing interleukins in response to infections by pathogens

fever has some benefits up to a point:

• slows down replication of bacteria and viruses as not at optimum temp

• increases production/activity of t cells

The Third Line of Defense

The Adaptive Immune Response targets specific pathogens and creates immunological memory, and involves leukocytes called B and T lymphocytes, present in the lymphatic system

lymphocytes

an agranular white blood ell that is important in the immune response: there are t lymphocytes and b lymphocytes

Adaptive Immunity

• acquired immunity: you develop it after an infection or immunization

• it is specific responding differently to each different type of pathogen

• response slower than innate

• effects are long lasting - immunological memory is produced (response to second+ encounters with same pathogen will be faster and stronger)

Hummoral Immunity

A specific response to foreign antigens which involves B lymphocytes that produce specific antibodies by plasma cells against extracellular antigens leading to the destruction of pathogens; also called antibody mediated immunity

Cell-mediated Immunity

A specific response involving cytotoxic T lymphocytes that targets intracellular pathogens (cells infected with viruses, cancerous cells and transplanted tissues)

Antigen Presenting Cells

Dendritic cells, macrophages and B cells digest and present antigen fragments linked to MHC 11 markers their cell membrane

• dendritic cells travel to lymph nodes, present complex to naive t helper cells which produce cytokines triggering adaptive response

Lymphatic System

a network of vessels and lymphoid organs that drain mph fluid from the tissues back into the circulatory system

Lymphatic system purposes

• a place of lymphocytes to mature

• transports lymphocytes, antigen presenting cells and antigens/pathogens to the lymph odes to stimulate AIR

what is the fluid that leaks from blood capillaries called

tissue fluid

some fluid that leaks from blood capillaries enter

lymph capillaries where its called lymph

• lymph moves through lymph vessels with the help of skeletal muscle contraction to eventually drain back into circulatory system

what does lymph vessel have

valves that prevent backflow, ensuring flow is one-way

primary lymphoid organs

• bone marrow

  • b and t cells made here

  • b cells matured here

• thymus

  • t cells matured here

Secondary Lympoid Organs

B and T cells are activated in the secondary lymphoid organs (lymph nodes, spleen, tonsils)

• lymph nodes located along lymph vessels

  • lymph passes through nodes on way back to bloodstream so antigens/pathogens trapped by macrophages her

• dendritic cells present antigens to t cells at lymph nodes, then clonal expansion

• memory cells stored here

T Cells

originate from stem cells in bone marrow, mature in thymus gland then differentiate into specialized cells (th cells and tc cells)

Helper T cells

Activated by recognizing MHC II + antigen on antigen presenting cells that secretes cytokines that activate T cells and B cells

Th CELLS DO NOT DEVELOP IN Tc CELLS

Cytotoxic T cells

Activated by cytokines from T helper cells that bind with and destroy non self eukaryotic cells, cancerous cells or cells infected with viruses by recognising MHC 1 + antigen presented on surface of self cells

T cell receptors

proteins made of two polypeptide chains.

• variable region

• constant region

• only one antigen binding site

Cell mediated immunity

• T cell activated from naive T cell when its receptor is bound by a complementary antigen-MHC II complex - clonal selection

• Activated T helper cell proliferates, creating clones with specific receptor matching the antigen - clonal expansion

• T cells differentiate into effector cells and cytokines are released or memory cells

• Th1: cytokines activate cytotoxic t cells promoting cl mediated immunity (intracellular)

• Th2: cytokines stimulate B cells to differentiate into plasma cells promoting humoral immunity (extracellar)

• release cytokines that help macrophages and NK cells

Memory T Cells

persist over a long period of time, speeds up response time upon secondary infection

T cytotoxic cells in cell mediated immunity

• after activated by cytokines from Th1, undergo clonal expansion

• move to bloodstream where they recognise MHC 1 and intracellular antigens (virally infected, bacterial, cancers)

• release perforin that forms holes in cell membranes and granzymes that enter through holes to induce apoptosis

• difference between NK cells is specificity

B cells

produced and matured in bone marrow

• fully activated b cells make antibodies

• defend against extracellular antigens

  • bacteria, fungi, protists - extracellular pathogens

  • free antigens (bacterial toxin

Humoral Immunity

• Clonal Selection: Naive B cells recognise a complementary antigen by direct binding n the lymph nodes which activates them.

• Clonal Expansion: B cell presented to activated T helper cell which releases cytokines that trigger expansion, creating clones with the same specific receptor matching the antigen

• B cell to differentiate into plasma cells and memory cells

Plasma B Cells

produces and secretes large numbers of highly specific antibodies against one specific antigen that help destroy them

Memory B cells

• remains in lymphoid tissue for long periods

• when they encounter the same foreign antigen again, they rapidly differentia into plasma cells

overall provides long lasting immunity and greater, faster response after a secondary exposure

Antibody

specific proteins that recognises and binds specific antigens, produced and secreted by plasma B cells

also called immunoglobulins

Features of an antibody

quaternary structure

constant region: the same for all antibodies of the same class

two identical variable regions enabling antibodies to nd to antigens

each antibody has two binding sites for the same antigen

Draw an Antibody!

Did you include:

• two heavy chains

• two short chains

  • connected by disulphide bonds

• constant region

• variable regions

Isotypes of Antibodies

IgM: most commonly produced at the beginning of an infection

IgE: involved allergic reactions

Antibody Function

• performs opsonisation

• neutralisation

• agglutination

• antibody bound to pathogens triggers the activation of the complement

Neutralisation

Antibodies bind to toxins and pathogen surface proteins preventing them from acting and blocking them from binding to their targets, and instead making them targets for phagocytosis

Agglutination

antibodies bind to antigens on two separate pathogens to form antigen-antibody complexes, which immobilizes (restricts movement) pathogens and attracts macrophages

Immunological Memory

Primary Immune response: response to the first encounter of a lymphocyte with an antigen. Memory T and B cells produced

Secondary Immune Response: results from subsequent encounters with the same antigen. Memory cells activated. lymphocyte and antibody production occurs much more quickly and response is more intense and longer lasting

• faster and greater

Active Immunity

develops in individual after exposure to antigen.

Antibodies and memory cells are made by the individual

develops over time but long lasting

Passive Immunity

acquired when antibodies are transferred from one individual to another

• protection immediate but temporary

Natural Active Immunity

random exposure to the pathogen in a natural setting

• cough

Artificial Active Immunity

deliberately introduced controlled first exposure to a pathogen

• vaccination

Natural Passive Immunity

a baby receives antibodies across the placenta or milk during breastfeeding

(baby has no immunological memory)

Artificial Passive Immunity

a person receives an injection of antibodies as a medical intervention

anti venom

monoclonal antibodies

Vaccination

deliberate introduction of weakened or dead foreign antigens into the body so that the body mounts an immune response that results in immunity (immunological memory) should the body be re-exposed

vaccine is a suspension of:

• attenuated pathogen (alive, usually virus)

• inactivated microbe (pathogen killed - might not look like pathogen ur infected with thus antibodies might not work), rabies

• toxoid (tetanus)

• subunit vaccine (part of a microbe likely to induce an immune response, coronavirus spike protein)

• mRNA that carries instructions for production of an antigen, enclosed in a lipid envelope, covid

booster vaccines

produces high levels of antibodies and circulating memory cells

• b/c memory B cell population drops overtime and gets below threshold to mount an effective immune response

Herd Immunity

A form of immunity against infectious disese where unvaccinated individuals are protected against a disease because a large number of people are vaccinated or are otherwise immune, thereby making it unlikely that unvaccinated people will come into contact with anyone suffering with the disease

• fewer susceptible hosts